Does Anyone Deserve to get Cancer?

It was not long ago that cancer carried a painful stigma. Patients afflicted with this terrible disease not only suffered with physical pain, but the emotional stress of what was once considered a “dirty” diagnosis. In my practice, I have often encountered patients from various cultures who ask that I not mention the word ‘cancer’ to their mother or father when I describe the treatments I must administer. In some countries, the cancer diagnosis is never mentioned and the treatment employed must, wherever possible, avoid the obvious features of cancer chemotherapy — like hair loss. Indeed, in some Asian countries, immune and nutritional therapies are more popular than chemotherapies as these allow patients to avoid the obvious side effects of cancer treatment.

While we in the U.S. consider ourselves “enlightened,” some of these attitudes persist within our culture, particularly with regard to cancers that had historically been associated with lifestyle or other exposures. Unfortunately, lung cancers and some cancers of the upper digestive tract are viewed in this way even today.

While cigarette smoking remains a principle causative factor in lung cancer, the percentage of men and women who smoke continues to fall while the incidence of non-smoking related cancers is on the rise. We are now witness to a growing realization that more than 20 percent of lung cancers occur in patients with distinct genetic predispositions unrelated to lifestyle or cigarette exposure. In addition, our increasingly polluted environment provides us all an unhealthy helping of carcinogens with almost every breath.

To suggest that lung cancer patients in some way constitute a population less deserving of our care and attention is an affront to the very principles of medical practice.

I, for one, find my increasingly good responses in lung cancer among my most gratifying successes. This heretofore untreatable malignancy is now revealing responses that challenge the successes in the “treatable” cancers like breast and ovarian. As some of our patients with metastatic disease are now alive at five and six years, we are certain that rationally delivered treatments can have the same beneficial impact upon this disease as any other. Every patient deserves the opportunity to receive the best, most effective, least toxic treatment. Our job is to match our patients with their best options, regardless of who they are, how they got the cancer or any contributing factors that may or may not have been responsible.

No one deserves cancer.

Why Doesn’t Rational Therapeutics do Gene Mutation Analyses?

Many patients inquire why we as a laboratory have not focused upon genomic analyses as part of the services we offer. There are several reasons why we have not focused on genomics. The first reason is that there are many laboratories that already commercially offer these analyses. These gene array methods can be automated and conducted comparatively cheaply. As we work hand-in-hand with many of the commercial purveyors of these techniques, we have seen little advantage in reproducing these methodologies in our facilities.

The second and more important reason that we have not pursued genomics reflects our belief that cancer is more complex than its gene signature. This point is critical to an understanding of what functional analyses are. We know that contained within the genes of each human is the information to create every protein, every enzyme, every lipid, every carbohydrate and all the organs and systems dependant upon their function. What we don’t know is how all of those 25,000+ genes are regulated to produce the unique features that constitute us as human entities.

From the moment of conception, when the male and female genetic materials are fused into what is known as a zygote, our informatics are established. What enables that single cell to become the multi-trillion-cell organism that we recognize as human is not the gene, but the gene regulation.

The informatics are static — the regulation, highly fluid.

Simply exploring the information contained within the human cell provides you with a blueprint of what may be, but no clear evidence that the outline structure will ever come to be in all of its functional complexity. In this regard, genomic analyses cannot approximate the vagaries and manifold variations that define us as individuals.

To look at this a different way, we can describe genetic information as “permissive, ” that is it tells you what you may or may not become. Functional information is “predictive,” it tells you exactly what you are. We have moved away from genomic analyses for the very reason that they provide only a veneer of information. The substance of cancer, its responsiveness to therapeutics and its ultimate cure, require a more definitive analysis. By studying human cellular behavior within the context of vascular, stromal and inflammatory elements, the EVA-PCD platform provides the closest approximation of human biology possible short of a clinical trial.

Human beings are demonstrably more than the sum of their genes. Cancer biology and the study of cancer therapy are many things, but simple is not one of them. Complex problems require solutions that incorporate all of their complexities, however uncomfortable this may be for genomic investigators.

Dr. Robert Nagourney Reacts to Surgeon General’s “One Cigarette” Report | FOX 11 News

Robert Nagourney, MD, responds to the new “One Cigarette” report. Is the claim that one cigarette is enough to cause cancer a reason to worry or is the report being taken out of context? Dr. Nagourney answers those questions and more on this segment.

Oncologist Reacts to Surgeon General’s “One Cigarette” Report | FOX 11 News.

Not Responding to the Standard Cancer Treatment? Maybe You’re an Outlier

In a recent reply to a blog comment, I mentioned the term “outlier” to describe a woman with breast cancer who had an excellent response to bevacizumab-based therapy. This was part of a discussion about the drug and its role in cancer treatment. The term outlier was utilized to describe this woman’s excellent response to a drug combination that has not achieved statistically significant survival advantage in the general population of breast cancer patients.

While outliers may connote strangeness or removal from the norm, in contemporary cancer therapies being removed from the norm can be a very, very good thing. After all, a minority of cancer patients benefit durably from chemotherapy. Those patients fortunate enough to have long-term responses are the happy outliers who populate the scientific community’s grab bag of anecdotes.

However, to the individual patient, a good response is much more than an anecdote, it is a life saving experience, an experience that every cancer patient richly deserves. While clinical trials are designed to identify average improvements for average patients, virtually every trial conducted has patients who live much longer than average. They constitute the tail on the survival curve and almost every trial has several.

Our job should be to identify those true responders and treat them appropriately rather than denying them active treatments based on the failure of the average patient paradigm. In statistics, the term applied for these failures are “beta errors,” meaning that the investigators missed the benefit of a given treatment. By identifying active treatments in small subsets of patients, functional analytic tools (like the Rational Therapeutics EVA-PCD platform) enable us to select those small subsets for treatment regardless of average expectations.

Novel Cancer Treatments — Crizotinib

Recent reports have described the striking activity of a novel Pfizer compound known as Crizotinib. The compound is an inhibitor of an enzyme known as the anaplastic lymphoma kinase (ALK). In approximately 5 percent of non-small cell lung cancer patients, a specific mutation known as the EML4-ALK rearrangement results in activation of this gene and the development of cancer. In those patients who are found positive for this mutation, the response rate to the drug Crizotinib is 57 percent with a disease control rate of 87 percent at eight weeks.

Hailed as an unprecedented response rate by Anil Potti, MD, associate professor of medicine at Duke University, these results reflect the power of pre-selection of candidates for treatment. The drug is reasonably well tolerated and represents a true advance. Taken in context, however, these results are not superior to those that we recently reported using conventional chemotherapies pre-selected by functional analysis. Indeed, our results with a response rate of 62 percent, a time to progression of 9.5 months and a median overall survival of 20.3 months are actually better. More notably, our results were obtained with conventional chemotherapeutics, not novel compounds.

What is most striking about the Crizotinib results is the capacity of pre-selection to demonstrably improve response rates. Yet, these results only apply to a distinct minority of patients. The results that we reported at ASCO reflect the activity of chemotherapy applicable to the remaining 95 percent of NSCLC patients. It is also highly likely that functional analysis will select Crizotinib candidates as well, or better, than the mutational analysis utilized for patient selection in the study reported. For comparison, our response rates for erlotinib (Tarceva) as a single agent are superior to the response rates for patients selected based on EGFR mutational analysis. In addition, secondary mutations have already been identified that confer resistance to Crizotinib, which likely confound durable remissions for this and related drugs.

While I applaud the results of this interesting trial, my team and I feel it important that all lung cancer patients have the benefit of pre-selection. Whether they fit into the 5 percent described in this report, or the 95 percent covered in our clinical trial.